Potassium Channels Flashcards

1
Q

What is the structure of a VG K+ channel alpha subunit?

A
Intracellular N terminus 
TM1
TM2
TM3
TM4
TM5
Pore loop
TM6
Intracellular C terminus
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2
Q

How many subunits come together for form a channel?

A

4
N terminal interacts with other alpha subunits
Typical of the same family e.g. Kv1.1 and kv1.1/kv1.2 etc

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3
Q

Why is TM4 of the alpha subunit important.

A

Contains a positive charged residue every 3rd amino acid (arginine or lysine)
Contributes to voltage sensitivity

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4
Q

What is a K+ channel antagonist?

A

Tetraethylammonium (TEA)

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5
Q

What TMDs are conserved across k+ channels?

A

5 and 6

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6
Q

What does the p loop contain?

A

The 30 amino acid selectivity pore

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7
Q

Why are k+ channels important?

A

Set RMP
Repolarisation
Conductance and cell time constants

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8
Q

The are 2 types of K+ channels…what are they?

A

Leak channels

Gated channels

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9
Q

What channels are in the category of leak channels?

A
Inward rectifiers (kir) which favour ion influx
Tandem pore outward rectifiers (K2P)
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10
Q

What types of k+ channels fall under the category of gated channels?

A
Volatage gated - conductance regulates AP Length
Ligand gated (e.g. By gpcrs, calcium, cyclic nucelotides)
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11
Q

What are some of the conduction properties of VG K+ channels?

A

Intracellular and extracellular entry ways lined with negative aminoacids
Pore length is 45A
Pore diameter varies throughout channel

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12
Q

What aminoacids are essential for k+ selectivity on selectivity pore?

A

Conserved GYG motif

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13
Q

What are the 4 mechanisms which allow k+ selectivity?

A

Helix dipole
Muiltple occupancy
Customised oxygen cages
Plenty of water

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14
Q

What is a helix dipole?

A

Positive to negative charged helix in pore to overcome electrostatic destabilisation
Lowers electrostatic barrier of membrane
Points towards centre of cavity

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15
Q

What does multiple occupancy allows for?

A

2 K+ in selectivity pore
1 K+ in cavity
Pushes ions through channel

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16
Q

What is the purpose of oxygen cages?

A

Co ordinate dehydrated K+ ions (must be dehydrated to pass through as internal helix creates hydrophobic environment)

17
Q

What cannot sodium ions fit through?

A

Sodium ions too small for perfect oxygen cage organisation

18
Q

What is the advantage of water for K+ selectivity?

A

Water in larger cavity stabilises ion and helps ion overcome electrostatic destabilisation due to low dielectric bilayer
In the centre of the bilayer polarising ability of ion lowest = high energy. Water helps minimise this

19
Q

What are the two types of channel inactivation?

A
N type (N terminal ball plugs channel)
C type (narrowing of the pore..contraction of outer mouth)
20
Q

What channels use N terminal inactivation?

A

Kv1.3 and kv1.4

21
Q

Where might the inactivation peptide be located?

A

May be in the alpha Or beta subunit of the potassium channel

22
Q

What do accessory subunits do?

A

Change the properties of the channel
E.g. Channel regulation, quicker inactivation (n terminal thether plug)
Kv1 (not kv1.4) is associated with beta1.1 subunit which increase inactivation through n terminal plug

23
Q

What is required for a single channel to open?

A

4 subunits need to be in the right state/confirmation to open properly
Open probability varies between individual channels but averaged together many channels from a united current as individual firing properties become negligible

24
Q

What kv channel is HVA?

A

Kv3 (opens at high levels of depolarisation)

25
Q

What kv channel is LVA?

A

Kv1+4

26
Q

What is the role of HVA channels?

A

Repolarisation of AP

27
Q

What is the purpose of LVA Kv channels?

A

Maintain RMP and regulate threshold for AP firing

28
Q

What is tetraethylammonium more selective for at low doses?

A

Kv3

29
Q

What is dendrotoxin selective for?

A

Kv1

30
Q

What channels set the RMP?

A

Leak channels - esp Tandem pore outward rectifiers e.g. k2P

31
Q

What happens if we increase the number of kv1 channels?

A

Will increase the threshold for AP firing as more will open at smaller depolarisations (more k+ efflux therefore more sodium needed to reach threshold)

32
Q

What would happen to an AP if we increased the number fo kv3 channels?

A

AP will be shorter as repolarisation will occur faster